Open Label, Single Ascending Dose, Cross-over Study to Assess the Pharmacokinetics of Circadin® (Prolonged-Release Melatonin) Mini Tablets in Children With Neurodevelopmental Disorders and Sleep Disturbances
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion
研究概览
简要总结
There is increasing evidence that chronic sleep disorders in children with autism spectrum disorder (ASD), Angelman Syndrome (AS) and Smith-Magenis syndrome (SMS) are associated with disturbed melatonin secretion and melatonin administration has been shown to be effective in these populations. For children who have difficulties swallowing a tablet, Neurim has developed an age-appropriate Melatonin formulation in the form of mini-tablets which have the same dissolution profile as the Circadin® tablets product, thus should produce the same melatonin concentration-time profile with the same effects. This study concerns the pharmacokinetic study.
The purpose of this study is to :
- Establish the 24 hour baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
- Establish the concentration-time profile of saliva melatonin concentrations and 24 hour 6-SMT urine excretion after 2 and 10 mg Circadin® mini-tablets single dose administration in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
- Evaluate the adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be 2 to 17 years old
- •Subject has a documented history of autistic spectrum disorder (ASD; as confirmed according to, DSM-IV-TR 299.00, 299.10 and 299.80 or ICD 10: F 84.0, F84.2, F84.3, F84.5, F84.9 ) or one of the following neurogenetic diseases according to ICD 10: Smith-Magenis syndrome, Angelman syndrome or Tuberous Sclerosis (Bourneville's disease)
- •Subject has current sleep problems; defined as difficulty initiating or maintaining sleep, or non restorative sleep, for at least 1 month (DSM-IV 307.42). Subject is able to comply with taking the study drug and collaborate freely with the study procedures;
- •Written informed consent from parents having parental responsibility or from the legal guardian(s). In the case of a child is aged 12 years or older the written informed consent of the child is needed in addition to that of parents having responsibility/legal guardian;
- •Subject is able to understand instructions in Dutch.
排除标准
- •Subject has history of difficulty with swallowing and/or easy choking;
- •Subject has current symptoms suggestive of obstructive sleep apnea syndrome or any breathing related sleep disorders or periodic limb movements;
- •Subject has known clinically significant disturbance(s) in hepatic and/or renal function;
- •Subject has non-stable epileptic attacks within 3 months prior to screening, in case of a history of epilepsy;
- •Subject who currently has asthmatic symptoms;
- •Subject has untreated medical/psychological condition that may be the etiology of sleep disturbances;
- •Subject is unable to refrain from the use of disallowed concomitant medication ordietary supplements (see paragraph 3.4) from 1 week prior to study occasions;
- •Subject is unable to refrain from caffeine-containing products for 24 hours before each occasion;
- •Subject has a known allergy to melatonin;
- •Female subject who is pregnant at time of screening;
- •Subject has unstable use of allowed medication within 2 months prior to the screening;
- •Subject has clinically relevant periodontal disease and/or oral injuries as judged by the investigator;
- •Subject is unable to refrain from eating bananas and chocolate during the entire day before saliva collection;
- •Subject is unable to refrain from drinks containing artificial colorants, caffeine (including but not limited to coffee, tea, cola), or alcohol during the day of the collection;
- •Subject is unable to refrain from aspirin or drugs that contain ibuprofen on the collection day;
- •Participation in an investigational drug study within 90 days prior to the first dose and/or participation in more than 4 clinical trials in the last year. -
研究组 & 干预措施
Circadin 10 mg
Second arm higher dose
干预措施: Circadin 10 mg (Drug)
Circadin 2 mg
First arm lower dose
干预措施: Circadin 2 mg (Drug)
结局指标
主要结局
baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion
时间窗: up to 1 year
To establish the 24 hour baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
concentration-time profile of saliva melatonin concentrations and 24 hour 6-SMT urine excretion after 2 and 10 mg Circadin® mini-tablets single dose administration
时间窗: up to 1 year
To establish the concentration-time profile of saliva melatonin concentrations and 24 hour 6-SMT urine excretion after 2 and 10 mg Circadin® mini-tablets single dose administration in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets
时间窗: up to 1 year
To evaluate the adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
次要结局
未报告次要终点